89 research outputs found
The prevalence of common mental disorders and PTSD in the UK military: using data from a clinical interview-based study
<p>Abstract</p> <p>Background</p> <p>The mental health of the Armed Forces is an important issue of both academic and public interest. The aims of this study are to: a) assess the prevalence and risk factors for common mental disorders and post traumatic stress disorder (PTSD) symptoms, during the main fighting period of the Iraq War (TELIC 1) and later deployments to Iraq or elsewhere and enlistment status (regular or reserve), and b) compare the prevalence of depression, PTSD symptoms and suicidal ideation in regular and reserve UK Army personnel who deployed to Iraq with their US counterparts.</p> <p>Methods</p> <p>Participants were drawn from a large UK military health study using a standard two phase survey technique stratified by deployment status and engagement type. Participants undertook a structured telephone interview including the Patient Health Questionnaire (PHQ) and a short measure of PTSD (Primary Care PTSD, PC-PTSD). The response rate was 76% (821 participants).</p> <p>Results</p> <p>The weighted prevalence of common mental disorders and PTSD symptoms was 27.2% and 4.8%, respectively. The most common diagnoses were alcohol abuse (18.0%) and neurotic disorders (13.5%). There was no health effect of deploying for regular personnel, but an increased risk of PTSD for reservists who deployed to Iraq and other recent deployments compared to reservists who did not deploy. The prevalence of depression, PTSD symptoms and subjective poor health were similar between regular US and UK Iraq combatants.</p> <p>Conclusion</p> <p>The most common mental disorders in the UK military are alcohol abuse and neurotic disorders. The prevalence of PTSD symptoms remains low in the UK military, but reservists are at greater risk of psychiatric injury than regular personnel.</p
Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients
<p>Abstract</p> <p>Background</p> <p>Radiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients.</p> <p>Methods</p> <p>Patients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication.</p> <p>Results</p> <p>A total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001).</p> <p>Conclusions</p> <p>Live lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.</p
Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms
Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin
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Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.
Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies
Deciphering the Chemical Basis of Nestmate Recognition
Social insects maintain colony cohesion by recognizing and, if necessary, discriminating against conspecifics that are not part of the colony. This recognition ability is encoded by a complex mixture of cuticular hydrocarbons (CHCs), although it is largely unclear how social insects interpret such a multifaceted signal. CHC profiles often contain several series of homologous hydrocarbons, possessing the same methyl branch position but differing in chain length (e.g., 15-methyl-pentatriacontane, 15-methyl-heptatriacontane, 15-methyl-nonatriacontane). Recent studies have revealed that within species these homologs can occur in correlated concentrations. In such cases, single compounds may convey the same information as the homologs. In this study, we used behavioral bioassays to explore how social insects perceive and interpret different hydrocarbons. We tested the aggressive response of Argentine ants, Linepithema humile, toward nest-mate CHC profiles that were augmented with one of eight synthetic hydrocarbons that differed in branch position, chain length, or both. We found that Argentine ants showed similar levels of aggression toward nest-mate CHC profiles augmented with compounds that had the same branch position but differed in chain length. Conversely, Argentine ants displayed different levels of aggression toward nest-mate CHC profiles augmented with compounds that had different branch positions but the same chain length. While this was true in almost all cases, one CHC we tested elicited a greater aggressive response than its homologs. Interestingly, this was the only compound that did not occur naturally in correlated concentrations with its homologs in CHC profiles. Combined, these data suggest that CHCs of a homologous series elicit the same aggressive response because they convey the same information, rather than Argentine ants being unable to discriminate between different homologs. This study contributes to our understanding of the chemical basis of nestmate recognition by showing that, similar to spoken language, the chemical language of social insects contains “synonyms,” chemicals that differ in structure, but not meaning
Somatostatin Inhibits Cell Migration and Reduces Cell Counts of Human Keratinocytes and Delays Epidermal Wound Healing in an Ex Vivo Wound Model
The peptide hormone somatostatin (SST) and its five G protein-coupled receptors
(SSTR1-5) were described to be present in the skin, but their cutaneous
function(s) and skin-specific signalling mechanisms are widely unknown. By using
receptor specific agonists we show here that the SSTRs expressed in
keratinocytes are functionally coupled to the inhibition of adenylate cyclase.
In addition, treatment with SSTR4 and SSTR5/1 specific agonists significantly
influences the MAP kinase signalling pathway. As epidermal hormone receptors in
general are known to regulate re-epithelialization following skin injury, we
investigated the effect of SST on cell counts and migration of human
keratinocytes. Our results demonstrate a significant inhibition of cell
migration and reduction of cell counts by SST. We do not observe an effect on
apoptosis and necrosis. Analysis of signalling pathways showed that somatostatin
inhibits cell migration independent of its effect on cAMP. Migrating
keratinocytes treated with SST show altered cytoskeleton dynamics with delayed
lamellipodia formation. Furthermore, the activity of the small GTPase Rac1 is
diminished, providing evidence for the control of the actin cytoskeleton by
somatostatin receptors in keratinocytes. While activation of all receptors leads
to redundant effects on cell migration, only treatment with a SSTR5/1 specific
agonist resulted in decreased cell counts. In accordance with reduced cell
counts and impaired migration we observe delayed re-epithelialization in an
ex vivo wound healing model. Consequently, our experiments
suggest SST as a negative regulator of epidermal wound healing
Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy
Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' — a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed
Comparative Analysis of Acinetobacters: Three Genomes for Three Lifestyles
Acinetobacter baumannii is the source of numerous nosocomial infections in humans and therefore deserves close attention as multidrug or even pandrug resistant strains are increasingly being identified worldwide. Here we report the comparison of two newly sequenced genomes of A. baumannii. The human isolate A. baumannii AYE is multidrug resistant whereas strain SDF, which was isolated from body lice, is antibiotic susceptible. As reference for comparison in this analysis, the genome of the soil-living bacterium A. baylyi strain ADP1 was used. The most interesting dissimilarities we observed were that i) whereas strain AYE and A. baylyi genomes harbored very few Insertion Sequence elements which could promote expression of downstream genes, strain SDF sequence contains several hundred of them that have played a crucial role in its genome reduction (gene disruptions and simple DNA loss); ii) strain SDF has low catabolic capacities compared to strain AYE. Interestingly, the latter has even higher catabolic capacities than A. baylyi which has already been reported as a very nutritionally versatile organism. This metabolic performance could explain the persistence of A. baumannii nosocomial strains in environments where nutrients are scarce; iii) several processes known to play a key role during host infection (biofilm formation, iron uptake, quorum sensing, virulence factors) were either different or absent, the best example of which is iron uptake. Indeed, strain AYE and A. baylyi use siderophore-based systems to scavenge iron from the environment whereas strain SDF uses an alternate system similar to the Haem Acquisition System (HAS). Taken together, all these observations suggest that the genome contents of the 3 Acinetobacters compared are partly shaped by life in distinct ecological niches: human (and more largely hospital environment), louse, soil
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease
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